Aryl ethanols are important intermediates in the manufacture of chemicals and pharmaceuticals. For example, 4-Hydroxyphenethyl alcohol (4-HPE) is useful as an intermediate in the preparation of several pharmaceutical compounds. U.S. Pat. No. 4,760,182 describes the use of 4-HPE to prepare phenoxypropanolamines, in particular the beta-adrenergic blocking agent, betaxolol. EP patent application No. 249,245 describes the use of 4-HPE for preparing the anti-hypertensiveagents,phenyl (dialkyl)dihydropyridine dicarboxylates. JP 86-201940 describes its use in preparing (aminopropoxyphenyl)alkanols and esters which are employed in the treatment of glaucoma.
Synthesis of 4-HPE has been documented in the past. Yamada et al. Chem. Pharm. Bill., (Tokyo), Vol. 11, pp. 258-260 (1963) describe its preparation from the corresponding amine, which, however, is not readily accessible. Khafagy et al. J. Med. Chem., Vol. 9(6), page 936 (1966) describe its synthesis from 4-hydroxyphenylacetic acid. Hussein, Angew. Botan., Vol. 38(1),pp. 1-43 (1964) reports its synthesis from phenethyl alcohol.
U.S. Pat. No. 5,003,115 (assigned to Hoechst Celanese Corporation) describes the production of 4-HPE from 4-acetoxystyrene.
There is a continuing interest in identifying improved and cost effective methods to prepare aryl ethanols such as 4-HPE, preferably from readily available materials or from materials that may be produced by simple and economical processes.
It has now been found that aryl ethanols can be prepared in high yields and in high purity from aryl methyl ketones, many of which are commercially available. The inventive process involves the oxidative conversion of aryl methyl ketones to ketoacetal derivatives, which can be hydrolyzed to glyoxals, which can then be reduced to aryl ethanols.